Colin L. Colby

Background: Data on respiratory syncytial virus (RSV) acute respiratory infection (ARI) among community-dwelling U.S. adults aged 18-64 years, particularly those with high-risk conditions (HRC), remain limited. This study estimated incidence and attack rates of RSV-ARI and RSV lower respiratory tract disease (LRTD) in adults with and without HRCs. Methods: A multi-state, community-based prospective cohort of adults aged 18–64 years with and without HRCs was followed from October 2022 to September 2024. Incidence rates and annual attack rates of RSV-ARI and RSV-LRTD were calculated by HRC presence and age group. Results: Of 3,375 adults with at least one HRC, the RSV-ARI incidence rate was 17.9 per 1,000 person-years (attack rates: year-1, 1.87%; year-2, 1.56%), compared with 14.8 per 1,000 person-years (year-1, 1.33%; year-2, 1.50%) among adults without HRCs. RSV-LRTD incidence was 10.0 per 1,000 person-years in adults with HRCs versus 5.7 per 1,000 person-years in those without. Asthma, congenital immunodeficiency, and immunosuppressive medication use were associated with increased incidence of RSV-ARI and RSV-LRTD; while adults with solid organ transplant and chronic kidney disease had a significantly higher incidence rate of RSV-LRTD compared to those without these conditions. Adults aged 18–49 years with HRCs had significantly higher RSV-LRTD incidence (9.6 vs. 4.3 per 1,000 person-years). After adjustment for age and sex, having ≥1 HRC was associated with a 62% increased RSV-LRTD risk, rising to 117% among adults aged 18–49 years. Conclusions: Adults with HRCs—particularly asthma, congenital immunodeficiency, chronic kidney disease, immunosuppressive medication use, and solid organ transplant—experienced higher RSV-ARI and RSV-LRTD incidence. The elevated RSV-LRTD burden was most pronounced in adults aged 18–49 years with HRCs.

Waldenström macroglobulinemia (WM) is characterized by recurrent MYD88 and CXCR4 mutations, whose prognostic value in patients treated with chemoimmunotherapy remains unclear. Moreover, the typically prolonged progression-free survival (PFS) correlates inconsistently with overall survival (OS), underscoring the importance of examining other surrogates. Progression of disease within 24 months (POD24), an established early end point, delineates functionally high-risk patients in other indolent lymphomas. This international study evaluated 253 patients receiving frontline fixed-duration bendamustine-rituximab (BR), a common chemoimmunotherapy for WM. At a median follow-up of 5.9 years, 5-year PFS and OS were 65% and 87%, respectively; 5-year PFS was similar between MYD88L265P (90%) and MYD88wild-type (WT) subcohorts (64% each; P = .4). Among 89 patients with known CXCR4 status, the subcohort with CXCR4mutation (28%) had shorter PFS (median 3.3 vs 8.8 years; hazard ratio [HR], 2.8; P = .0036) and OS (HR, 2.6; P = .036) compared with CXCR4WT. POD24 occurred in 11.5% of patients who demonstrated inferior subsequent OS (5-year OS, 71% vs 86%; HR, 3.1; P = .005) and higher mortality (standardized mortality ratio [SMR], 3.7), unlike the non-POD24 group, whose mortality was comparable to the matched general population (SMR, 1.1). In conclusion, BR is effective irrespective of the MYD88 status, but CXCR4 mutations and POD24 portend worse outcomes. Patients without POD24 represent a cohort with distinctly favorable outcome.

Naltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; ≥5 drinks for men, ≥4 drinks for women in a day), during the first three months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N=1090 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p=1.6E-08) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p=3.9E-08; acamprosate TR: rs77583603, p=3.1E-09). The top association signals for TR (p=7.7E-08) and second strongest signal in the THR (p=6.1E-08) analysis of the naltrexone-treated subset map to PTPRD , a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p=3.7E-04) and THR (p=2.6E-04). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.